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Molecular And Cell Biology
David Presti

Pharmacology; terminology and history Drug = exogenous chemical which in relatively small amounts has effects on physiology i.e. on the functioning of an organism. Dried/dried plant “droog”? Psychoactive drug – chemical that has effects on human behavior (actions, mental processes) via its effects on the nervous system Pharmacology = a study of how drugs interact with the body i.e. absorption, distribution, mechanisms of action Psychopharmacology = study of how psychoactive drugs have an effects on the body and mind Pharmako = medicine and poison Ethnobotany = study of relationships between plants that have ethnobotanical importance to indigenous people (study of plant medicines) Power plants, allies, plantas maestras, allies = plants have the power to teach and help Old world; cannabis, tea, coffee, opium, spices New world; tobacco, cocoa, cacao “War on drugs” = war against plants - Power plants, knowledge from plants - Dangerous/forbidden - Severe punishment 1.9 million drug arrests/year 600 000 violence arrests 1.5 mil property crime arrests. Healers; - Shaman = Central Asia, “one who is excited, moved, raised” - Curandero, curandera = Latin America - Witch doctor, medicine man/woman/sorcerer, wizard, magician - One who has mastered spirits, one who can use the power of spirits to help people Paracelsus (1493-1541) - Theophrastus Phillippus Aureolus Bombastus von Hohenheim - Physician, scientist, chemist, alchemist, philosopher - Chemical urinalysis - Administration of specific medicines, remedy - Proposed methods for treating wounds and preventing infection - Appreciated the connection between mental states and physical properties of a body • "All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy." - Higher state funding for correctional facilities over the past 30 years. How drugs enter the brain Drug -> Body -> Blood -> Brain Routes of administration Oral : ingestion by mouth, enters stomach and intestines. The hepatic portal system connects the intestines and the liver. It consists of vessels that carry blood from the stomach and intestines to the liver. - Liver detoxifies the blood - This is called the first pass metabolism and possible biotransformation may occur. TIME TO BRAIN = APPROX. 20 MINUTES Other routes of entry; - Bypass the digestive system - Increased speed of onset - Chemical intactness Parenteral routes  “par” = beyond  “enteron” = intestines Intraoral: absorption in the mouth (not swallowed); buccal (cheek), sublingual (tongue). - Many little blood vessels in the mouth therefore TIME TO BRAIN = 3 MINUTES Intranasal; absorption in the nasal mucosa; insufflation; snorting - Goes to general circulation before brain TIME TO BRAIN = 3 MINUTES Rectal; e.g. suppository, enema; rich in blood vessels TIME TO BRAIN = 3 MINUTES Transdermal; across the skin, contact absorption e.g. patch medications TIME TO BRAIN = MANY MINUTES TO HOURS depending on patch Inhalation ; smoking; vapors, gases, pyrolyzed (burned for smoking) substances - This is the fastest route to the brain under ordinary conditions because the lungs are full of blood vessels TIME TO BRAIN = 10 SECONDS Injection; using hypodermic syringe  Intravenous (IV) o Directly into blood vessel TIME TO BRAIN = 20 SECONDS  Intramuscular (IM) TIME TO BRAIN = 3 MINUTES  Intraperitoneal (IP) o Injected into the abdominal area TIME TO BRAIN = 3 MINUTES  Subcutaneous (sub Q) o Slow, steady absorption TIME TO BRAIN = MANY MINUTES Injection is most efficient for water-soluble substances - Most dangerous if not in medical use (overdose risk) - Rapid entry of large dose Elimination from body; Excretory mechanisms -> liver, blood, kidneys, bladder, urine. If absorbed slowly, it is gradually distributed. Conc. Of drug in the blood Time of effect Blood-brain barrier = tight junctions between cells forming blood vessel walls, it is crossed by transport and diffusion Passive transport of needed molecules (glucose, amino acids) and diffusion of sufficiently hydrophobic molecules Al Kamia; ancient Egypt -> black earth land rich, fertile, creative, transformative Molecules = atoms joined together by covalent chemical bonds (shares a pair of electrons) The brain = most complex structure; contains 10 nerve cells and 10 glia cells. DOPAMINE SEROTONIN Agonist = molecule that binds to a neurotransmitter receptor and activates it Antagonist = molecule that binds to a neurotransmitter receptor and blocks it. CNS = Central nervous system, consists of brain and spinal cord Somatic Nervous system = muscle, sensory, enteric (in the gut) Autonomic NS = reflexes CNS somatic autonomic Autonomic nervous system Sympathetic • Increases heart rate • Increases blood pressure • Dilates lung airways • Dilates pupils of eyes • Constricts bladder • Decreases intestinal motility NT = norepinephrine Parasympathetic • Decreases heart rate • Decreases blood pressure • Constricts lung airways • Constricts pupils • Stimulates bladder • Stimulates intestinal motility NT = acetylcholine Sympathomimetic = drugs that activate/enhance activity of the sympathetic nervous system e.g. cocaine Sympatholytic = drugs that inhibit/disrupts activity of the sympathetic nervous system Parasympathomimetic = drugs that activate/enhance activity of the parasympathetic nervous system e.g. cocaine Parasympatholytic = drugs that inhibit/disrupts activity of the parasympathetic nervous system Carl von Linne (Linnaeus) (1707-1778) - Popularized the Latin binomial naming system Solanaceous plants “Solamen” = quieting Funnel shaped, five fused petals e.g. Angel’s trumpet, tomato, potato, eggplant, chilli Mostly from South America *See list* Alkaloid = organic chemical that contains a basic nitrogen atom Plants containing tropane alkaloids; atropine (hyoscyamine) and scopolamine. - Alkaloids often have a bitter taste - Alkaloids are poisons o Innate aversion to bitterness? Can be overcome by learning to appreciate it. Evolved avoidance tendency? - Plants may manufacture alkaloids as a defense against insects and other predators 2 major types of acetylcholine receptor; - Muscarinic; brain, parasympathetic system (responds to muscaine) - Nicotinic; brain, neuromuscular system (responds to nicotine) Atropine and scopolamine are muscarinic acetylcholine receptor antagonists  They reduce activity in the parasympathetic NS  Therefore have parasympatholytic effects Uses in contemporary medicine; - Slow intestinal motility - Treatment of irritable bowel syndrome - Intestinal cramps, diarrhea - Pupil dilation for eye exams - Asthma - Anti-motion sickness Tropane alkaloids now often replaced with less poisonous, synthetic drugs, atropine is no longer used. CNS effects; - Impaired memory, amnesia - Dreamy state of consciousness, hallucinations - Disorientation/confusion Hallucination- “hallucinari” = to wonder in the mind - Perceptual experience in the absence of relevant sensory stimuli - Compelling, often not under willful control and cant be treated easily James I King of England (1566-1625) - Declared tobacco trade with America to be a royal monopoly and taxed it heavily - “Counterblaste to Tobaco” Jean Nicot (1530-1600) - French Ambassador learns about tobacco from a Portuguese botanist and brings it to France Sir Walter Raleigh (1552-1618) - Tobacco aficionado - James I ordered him executed George Washington - Farmer, grew some tobacco - Grew cannabis for hemp - Opened distillery (whiskey) Tobacco and Nicotine Nicotiana tabacum = primary domesticated species of tobacco Nicotine is the primary psychoactive alkaloid from tobacco, isolated from tobacco in 1828 *Main effect = agonist at nicotinic acetylcholine receptors Acute (short term) effects; - CNS stimulant and relaxant - Increased alertness and focus of attention - Anxiolytic/grounding - Enhanced REM sleep and dreaming - Increased heart rate and blood pressure - Increased metabolic rate - Nausea, vomiting o Triggers clusters of cells in the brain to induce nausea i.e. in first time smokers, low tolerance LD-50 = lethal dose for 50% of the population, around 60mg for humans Tolerance develops to many of the toxic effects of nicotine e.g. nausea, increased heart rate and dizziness Mortality; around 430 000 deaths/year compared to total annual US deaths of 2.3 mil. Toxic effects of tobacco use on health: Cardiovascular effects of nicotine • Increased heart rate, vasoconstriction, and blood pressure • Chronic cardiovascular stress • May precipitate or exacerbate cardiac arrhythmia, chronic hypertension, atherosclerosis • Peripheral vascular disease • Increased occurrence of heart attacks and strokes Effects of carbon monoxide in blood • Carbon monoxide is extremely poisonous • Gut-competes oxygen for binding to hemoglobin in red blood cells • Reduced oxygenation of entire body (hypoxia) Effects of tobacco smoke on lungs • Smoke contains numerous irritant and carcinogenic molecules • “Tars” ~ polycyclic aromatic hydrocarbons • Increased risk of respiratory infections, chronic bronchitis, COPD (chronic obstructive pulmonary disease), •emphysema, lung cancer • Increased risk of cancers of mouth, throat, larynx Fetal development and neonatal health - Women who smoke are less fertile - 50% lower chance of pregnancy - 50% increased risk for spontaneous abortion - “Fetal tobacco syndrome” o Higher % premature birth o Perinatal mortality o Unexplained neonatal death First cigarette package warnings were introduced in 1966. Strengthened package warnings introduced in 1970 and 1985 Graphics proposed in 2009 To be implemented Fall 2012 Tobacco companies vs. FDA “Compelled speech” August 2011 = Lawsuit November 2011 and Feb 2012 = Rulings Feb 2012 = FDA appeals, reissue implementations Aug 2012 = Federal appeals court ruling Second-hand smoke • Environmental tobacco smoke (ETS) • Passive smoking • Side-stream smoke Associated with increases in: • Cardiovascular disease • Lung disease • Asthma, bronchitis, pneumonia (especially in children) • Low birth-weight infants • Sudden infant death syndrome (SIDS) • > 35,000 deaths / year in USA Addiction; uncontrolled relationship - Most people who smoke tobacco at all are daily smokers - Most who attempt to quit have a difficult time quitting Nicotine withdrawal;  Irritability  Nervousness/anxiety/restlessness  Difficulty concentrating  Depressed mood  Insomnia/sleep disturbances  Increased appetite/weight gain High addictive potential due to pharmacologic and psychosocial factors - Does not interfere with functioning - Easy to obtain, accepted in society - Heavily and sexily advertised Reinforcing/rewarding aspects of tobacco use; - Mental stimulant - Grounding/calming - Rapid delivery to brain *MINDFUL YOGIC ATTENTION TO THE BREATH; sensual breathing Quitting • Decide positively that you want to quit • Pick a specific quit date • Tell others about your plan • Conduct a quitting ritual • Throw away your cigarettes and other paraphernalia • Plan ways to deal with cravings • Avoid tempting situations • Learn and practice new skills and behaviors • Get support and encouragement • Reward yourself for not smoking • Be prepared for relapse Pharmacologic aids to quitting • Nicotine replacement therapies • Over-the-counter = nonprescription: • Nicotine gum • Nicotine patch • Prescription required: • Nicotine nasal spray • Nicotine inhaler • Bupropion (antidepressant) • Wellbutrin® and Zyban® • Dopamine and norepinephrine reuptake inhibitor, nicotinic ACh receptor antagonist • Chantix® = varenicline tartrate • Nicotinic acetylcholine receptor agonist (weaker agonist than nicotine) • All of these pharmacologic aids work better when coupled with behavioral programs of education, support, and skills development 2009 - Congressional bill giving the FDA (Food and Drug Administration) greater power to regulate tobacco • Bans flavored cigarettes (menthol excepted) • Advertising restrictions on using “light,” “low-tar,” and “mild” Prevalence = % of population affected with a particular condition or engaging in a particular behavior Pituri - Duboisia hopwoodii - Native to Australia, Solanaceous - Contains nicotine - Leaves are roasted, chewed, sometimes smoked - Australian aborigine culture  Rattles used in rituals as tools by shamans Highest prevalence of use of cigarettes in the US ages; 18-29 27.7% US tobacco products for people >12 23.3% US cigarettes for people >12 *Current tobacco use by education level. Huge impact from education on cigarette use, a good predictor of cigarette smoking $150 billion per year Auto accidents; approx. 50% alcohol related Suicides; approx. 30% alcohol related Mortality in the US; approx. 150 000 per year  Lower than tobacco “Gin Lane” engraving by William Hogarth, 1751 tries to recapture consequences (adverse) of alcohol consumption Prevalence of alcohol abuse in general medical practice Outpatient; approx. 15% Inpatient; approx. 40% Chronic medical problems associated with alcohol abuse - Liver problems o Fatty liver, hepatitis (pores in liver and hurts), cirrhosis (scarring, reduces ability of liver to clean toxins out of blood) - Pancreatitis (inflammation - Gastrointestinal problems - Cardiovascular problems - Nervous system problems o Peripheral neuropathy o Cerebral atrophy o Cognitive impairment Brain trophy occurs with chronic heavy alcohol consumption - Larger ventricles (smaller brain tissue volume) in smaller corpus collosum in alcoholics Teratogenic effects of alcohol on fetal development; - Fetal Alcohol Syndrome (FAS) - Fetal Alcohol Effects (FAE) - Prenatal and post natal growth retardation - Malformations of facial structure - CNS abnormalities; mental retardation, attention deficits, other behavioral problems Alcohol use by pregnant women; Any use during the past month = pregs 12%, non-pregs 53% Binge drinking during the past month = pregs 4%, non-pregs 23% *Warning label on alcoholic beverages sold in the US Heath effects of light alcohol use (less than 1-2 drinks/day) GOOD: Increased HDL, decreased LDL, decreased atherosclerosis, decreased heart attack risk BAD: increased cancer risk (female breast, oral, esophageal) How alcohol works in the brain GABA (gamma-amino-butyric acid) Major inhibitory neurotransmitter in the brain Ethanol facilitates/enhances GABA action at GABA receptors Results in global CNS inhibition Glutamate Major excitatory neurotransmitter in the brain Ethanol antagonizes glutamate receptors Magnifies inhibition, decreases excitation Adenosine Inhibitory neurotransmitter Ethanol blocks presynaptic reuptake of adenosine  Alcohol is a sedative-hypnotic drug o Sedate = to calm o Hypnos = to sleep Sedative-hypnotic withdrawal - Anxiety, tremor, increased heart rate, increased blood pressure Severe symptoms; hallucinations (auditory, visual, tactile), delirium (confusion, disorientation), agitations, severe autonomic instability, seizures. Sedative-hypnotic drugs; - Alcohol - General anesthetics e.g. diethyl ether, halothane, enflurane o Global loss of sensation vs. local anesthetics - Inhalants; huffing of petroleum distillates - Barbiturates; low TI, used in lethal injection - Benzodiazepines; higher TIs, widely used • Other sedative hypnotics: Quualude, Ambien, propofol... • Sedative hypnotics facilitate GABA action • Addictive potential of sedative-hypnotics Plants with sedative-hypnotic properties; - Absinthe - Wormwood: Artemisia absinthium Inhalation general anesthetics; halogenated hydrocarbons and ethers Sedative-hypnotic neurochemistry: Facilitate GABA action at GABA recepAors Addiction = inability to control one’s use - Often associated with withdrawal effects, usually associated with adverse consequences - Sedative-hypnotic drugs have a significant potential for addiction Some plants with potential anxiolytic and sedative-hypnotic properties • Kava (Piper methysticum) • Valerian (Valeriana officinalis) • Chamomile (Matricaria recutita) • Lavender (Lavandula augustifolia) • Catnip (Nepeta cataria) • Hops (Humulus lupulus) • Passionflower (Passiflora incarnata) • Linden (Tilia europaea) Absinthe (from the Greek word “apsinthion” = undrinkable) - *Wormwood (Artemisia absinthium) o Hyssop (Hyssopus officinalis) o Lemon balm (Melissa officinalis) o Anise (Pimpinella anisum) o Fennel (Foeniculum vulgare) o Other herbs - Bitter - Use of absinthe spoon o Sugar cube to lessen bitterness o High alcohol level o Pour water through to dissolve sugar and dilute the absinthe - Transparent when pure, becomes cloudy when added with water o Due to presence of oily things that dissolve better in alcohol than water o Cloudy because of tiny oil droplets Current legal status of absinthe: - Legal again throughout the EU - Thujone <35mg/l  FDA; products for human consumption must be free of thujone o Sold in the USA since 2007 o Claim that thujone <10mg/l (10 ppm)  Thujone is a GABA receptor antagonist and CNS stimulant Drug abuse = use of a drug that leads to adverse consequences, may be severe or subtle Brief history of drug Laws 1791 Whiskey Tax and Whiskey Rebellion (1794) • Federal tax imposed on distilled spirits to raise money to reduce federal debt • Opposition squelched using military force 1906 Pure Food and Drug Act • Improvements in labeling and to prevent the writing of misleading labels 1914 Harrison Narcotics Act • Regulated the importation, manufacture, and sale of opium, coca, and their derivatives • Physicians arrested for prescribing narcotics to addicts (1920s) 1920 Eighteenth Amendment to the US Constitution • Proposed by Congress in 1917, ratified by the states completed by 1919 • Prohibits the manufacture, sale, and transport of alcoholic beverages 1930 Bureau of Narcotics established • Headed by Harry J. Anslinger (1892-1975); he retired from this position in 1962 1933 Twenty-first Amendment to the US Constitution • Repeals the 18th Amendment: alcohol prohibition ends 1937 Marijuana Tax Act • Provided for penalties for the untaxed possession of marijuana 1956 Narcotic Drug Control Act • Imposition of mandatory minimum sentences • More severe penalties implemented, including death penalty for selling heroin to a person under 18 1970 Controlled Substances Act (CSA) • Replaced all previous federal laws concerned with “dangerous drugs” • Comprehensive categorization of all psychoactive drugs deemed to have abuse potential 1971 United Nations Single Convention on Psychotropic Substances • International adoption of controlled-substance categorization 1973 Drug Enforcement Administration (DEA) established • Replaced and consolidated the Bureau of Narcotics and other federal agencies 1984 Comprehensive Crime Control Act • Established sentencing guidelines based on drug type and quantity • US Sentencing Commission established Federal Controlled Substances Schedules Schedule I - No currently accepted medical use in the US - Lack of accepted safety for use under medical supervision - High potential for abuse Gamma-hydroxybutyrate (GHB) (provision for Schedule III when used in clinical application or research) Tetrahydrocannabinols Preparations, resins, or extracts of substances contained in the Cannabis plant - (e.g., marijuana, hashish)  E.g. heroin, amphetamine analogues, various opiates, all psychedelics/hallucinogens Schedule II - High potential for abuse - Abuse may lead to severe psychological or physical dependence  E.g. raw opium, opium poppy, most opioids (Papaver sonniferum), morphine, codeine, hydromorphine, cocaine Schedule III - Potential for abuse less than substances in schedules 1 and 2 - Abuse may lead to high psychological or low-moderate physical dependence  E.g. certain opioids and opioid combinatorics, Tylenol (acetaminophen with codeine), anabolic steroids Schedule IV - Potential for abuse less than substances in schedule 3 - Abuse may lead to limited physical or psychological dependence relative to substances in schedule 3  E.g. all benzodiazepines, sedative-hypnotics, Valium, Librium, Xanax, Ativan Schedule V - Lower abuse chances than schedule 4  E.g. codeine cough syrups, diphenoxylate, pregabalin Substances in all other schedules (II - V) all supposedly have currently accepted medical uses in the United States The schedules are more of a political than a scientific category. Prescribing controlled substances in schedules II-V requires specific permission from the DEA, prescribing schedule II controlled substances is more strictly regulated in some states. Notable omissions from CSA scheduling: nicotine / tobacco and alcohol - From the “Definitions” section of the Federal CSA: The term “controlled substance” means a drug or other substance, or immediate precursor, included in schedule I, II, III, IV, or V of part B of this subchapter - The term does not include distilled spirits, wine, malt beverages, or tobacco, as those terms are defined or used in subtitle E of the Internal Revenue Code of 1986. Federal versus State: Uniform Controlled Substances Act of 1970 - Agreement among the 50 states to adopt essentially copies of the federal law to apply in each of the states - Each state has its own version of the controlled substance act with corresponding drug schedules - Most states simply copy the federal schedules - Some states may schedule certain drugs that are not in the federal schedules - Some states have placed substances into Schedule I that are not in Schedule I federally - Flunitrazepam (Rohypnol) is Schedule I in Idaho, Minnesota, and Oklahoma - Salvia divinorum is Schedule I in 17 states, with legislation pending in others (August 2011) - Medical marijuana laws passed by 16 states and DC (as of August 2011) are essentially propositions to effectively remove marijuana from Schedule I o Alaska, Arizona, California, Colorado, Delaware, DC, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, Washington Such proposals have not been recognized by the federal government and marijuana continues to be treated as an illegal Schedule I substance by federal authorities, regardless of state law Schedule II substances require stricter prescribing control in some states For example: no automatic refills, no oral/phone prescriptions (written required) - Several states have triplicate prescriptions for Schedule II substances - Third copy goes to a state agency which tracks prescribers and patients - In state of Washington, tracking only required of prescribers who have been previously disciplined - Triplicate prescription requirement in California ended Jan 2005 - Replaced by “security prescription forms” for all controlled substances  In general, system is moving toward database tracking of all controlled substances CONTROLLED SUBSTANCE ANALOGUES (sometimes called "designer drugs") • Fentanyl analogues sold as “synthetic heroin” late 1970s - early 1980s • Resulted in several overdose deaths because of unexpectedly high potency • Not illegal at the time, as they were new compounds, not listed in the CS Schedules • This inspired the development of additional drug regulations, as described below CONTROLLED SUBSTANCES ANALOGUE ENFORCEMENT ACT (1986) • Also known as the “Designer Drug Bill” • Allows for the prosecution of any act associated with an unscheduled drug, if that drug is analogous in structure and action to a Schedule I or II drug Controlled Substance Analogue = a substance where the chemical structure of which is substantially similar to the chemical structure of a controlled substance in schedule I or II which has a stimulant, depressant, or hallucinogenic effect on the CNS that is substantially similar to or greater than the stimulant, depressant, or hallucinogenic effect on the CNS of a controlled substance in schedule I or II, with respect to a particular person, which such a person represents or intends to have a stimulant, depressant, or hallucinogenic effect on the CNS of a controlled substance in Schedule 1 or 2. To the extent such a controlled substance analogue is intended for human consumption, it shall be treated as a schedule I controlled substance.  Exemption is made only for drugs that have been cleared by the FDA by a new drug application.  There is no objective standard for what is meant by the phrase “substantially similar” in the legal definition of a controlled substance analogue, there is no connective (“and” or “or”). EMERGENCY SCHEDULING ACT - Provides for rapid placement into schedule I of drugs not previously listed in any schedule - No judicial review necessary - Emergency scheduling of such a drug would expire after 18 months o In the interim, hearings can be held to place the drug into schedule I on a permanent basis - Recent application of ES has been applied to several synthetic psychedelic compounds - Most recent temporary additions to schedule I are several synthetic cannabinoid- receptor agonists • JWH-018, JWH-073, JWH-200 • CP-47497, CP-47497 C8 homolog • Have been sold as “Spice” and “K2” etc. - These are in final stages of permanent placement into Schedule I UPDATES ON CONTROLLED SUBSTANCES • New compounds are regularly added to the controlled substance schedules • A comprehensive listing of currently scheduled substances can be found on the website of the United States Drug Enforcement Administration (DEA) • The most comprehensive information source regarding controlled substances and scheduling: Cannabis Cannabis have originated from central Asia – Afghanistan and carried everywhere. Afghanistan was at one time famous for producing cannabis of the highest quality Cannabis has been used by humans for thousands of years for its medicinal and psychoactive properties. - Analgesia (relief from pain - Anti-inflammatory - Anti-spasmodic (muscle relaxant) - Appetite stimulant - Antiemetic (relief from nausea/vomiting) - Reduces intraocular pressure (treats glaucoma) - Anti-seizure/anti-convulsant - Sedative (relaxant) - Hypnotic (induces sleep) - Psychedelic-like mental state Routes of administration - Oral/digestive - Inhalation of smoke from incense o Later; pipes, cigarettes Known as: marijuana, pot, grass, weed, ganja, bhang Possible species; sativa, indica, ruderalis Concentrated resin = hashish, hash “Temple balls” highest quality hashish – Nepal Cannabis for fiber; rope, cloth, paper – may have been the oldest historical use • “hemp” (English) • From “hanaf” (German) • From “cannabis” (Latin) • From “kannabis” (Greek) • The word “canvas” derives from cannabis George Washington was a hemp farmer and so was Thomas Jefferson Benjamin Franklin owned a hemp paper mill. Cannabis is nutritious – seed is high in omega-3 fatty acids, contributors to cardiovascular and neural health. Possible psychological/mental effects of Cannabis: - Varies with user’s mental set; expectations, prior experience, personality, current state of mind and physical setting May be psychedelic-like (mind manifesting) - Enhanced/altered sensory perception - Intensification of emotions and thoughts - Altered sense of self - Sedation/relaxation - Heightened anxiety/panic o Intensification of emotions o Weakening of psychological defenses - Impaired short-term memory; storage of new information - Altered sense of time (probably related to memory effects) William James (1842-1910) “The Principles of Psychology” talks about hashish Possible physiological effects of Cannabis - Reddening of eyes, from dilation of blood vessels - Increased heart rate (mechanism not known) - Decreased salivation - Decreased lacrimation (tearing) - Increased appetite (“munchies”) - Slowed reaction time and impaired coordination o Sensual enhancement/aphrodisiac effects Toxicity of cannabis smoke; high levels of toxins (lung damage/cancer risk?) Addiction/dependence: Delta-9-tetrahydrocannabinol - Primary psychoactive chemical in cannabis - Identified by Raphael Mechoulam in 1964 using “dog ataxia” test i.e. what dosage it takes for the dog to fall over - THC does not have a nitrogen atom therefore isn’t an alkaloid Cannabinoid chemistry: - Unique chemical structure, found nowhere else (over 60 identified) - Cannabinol (CBN) - Cannabidiol (CBD) - Delta-9-tetrahydrocannabinollic acid o THC contained throughout plant o Highest concentration in the bud resin - High-potency preparation - “Sinsemilla” = without seeds - THC concentration <1% to >>10%  City of Oakland sues US Department of Justice (Oct. 10 2012) o Dept. of Justice attempts to close down marijuana dispensaries. Oregon Cannabis Tax Act (Measure 80) • Cannabis grown under license and taxed • Regulated sales to age 21+ buyers and medical-prescription holders • Hemp deregulated and allowed to be grown commercially • Promotion of hemp industry for fiber and as biofuel • State Attorney general authorized to defend against federal challenges Colorado The Regulate Marijuana Like Alcohol Act of 2012 (Amendment 64) • Provides for licensing of cultivation, processing, testing, and sales facilities • Permits sales to and possession of less than one ounce for age 21+ • Separates Hemp off of other Cannabis products for regulatory purposes • Hemp = THC < 0.3% • Calls for legislation to be developed by 2014 to govern the cultivation, processing, and sale of hemp Washington On Marijuana Reform (Initiative 502) • Licensed cultivation and sale of cannabis to age 21+ buyers Historical Background: 2010 Election California Proposition 19: Regulate, Control, and Tax Cannabis Act Defeated 53.5% to 46.5% 1996 Election California Proposition 215: Medical Marijuana Passed 55.6% to 44.4% THC is hydrophobic and therefore is somewhat an oily substance which dissolves into the phospholipid bilayer of the cell membrane and “sticks around”  Slow excretion of lipid-soluble metabolites from body o Marijuana stays for quite relativel
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